Intensity modulated radiotherapy (IMRT) in patients with carcinomas of the paranasal sinuses: clinical benefit for complex shaped target volumes

INTRODUCTION: The aim of the study was to evaluate the clinical outcome of intensity modulated radiotherapy (IMRT) in 46 patients with paranasal sinus tumors with special respect to treatment-related toxicity. PATIENTS AND METHODS: We treated 46 patients with histologically proven tumors of the paranasal sinuses with IMRT. Histological classification included squamous cell carcinoma in 6, adenocarcinoma in 8, adenoidcystic carcinoma in 20 and melanoma in 8 patients, respectively. Six patients had been treated with RT during initial therapy after primary diagnosis, and IMRT was performed for the treatment of tumor progression as re-irradiation. RESULTS: Overall survival rates were 96% at 1 year, 90% at 3 years. Calculated from the initiation of IMRT as primary radiotherapy, survival rates at 1 and 3 years were 95% and 80%. In six patients IMRT was performed as re-irradiation, and survival rate calculated from re-irradiation was 63% at 1 year. Local control rates were 85% at 1, 81% at 2 and 49% at 3 years after primary RT and 50% at 1 year after re-irradiation. Distant metastases-free survival in patients treated with IMRT as primary RT was 83% after 1 and 64% after 3 years. For patients treated as primary irradiation with IMRT, the distant control rate was 83% at 1 year and 0% at 2 years. No severe radiation-induced side-effects could be observed. CONCLUSION: IMRT for tumors of the paranasal sinuses is associated with very good tumor control rates. Treatment-related acute and long-term toxicity can be minimized as compared to historical results with conventional RT

Complete genome sequence and analysis of Wolinella succinogenes

To understand the origin and emergence of pathogenic bacteria, knowledge of the genetic inventory from their nonpathogenic relatives is a prerequisite. Therefore, the 2.11-megabase genome sequence of Wolinella succinogenes, which is closely related to the pathogenic bacteria Helicobacter pylori and Campylobacter jejuni, was determined. Despite being considered nonpathogenic to its bovine host, W. succinogenes holds an extensive repertoire of genes homologous to known bacterial virulence factors. Many of these genes have been acquired by lateral gene transfer, because part of the virulence plasmid pVir and an N-linked glycosylation gene cluster were found to be syntenic between C. jejuni and genomic islands of W. succinogenes. In contrast to other host-adapted bacteria, W. succinogenes does harbor the highest density of bacterial sensor kinases found in any bacterial genome to date, together with an elaborate signaling circuitry of the GGDEF family of proteins. Because the analysis of the W. succinogenes genome also revealed genes related to soil- and plant-associated bacteria such as the nif genes, W. succinogenes may represent a member of the epsilon proteobacteria with a life cycle outside its host

Longitudinal immune profiling reveals key myeloid signatures associated with COVID-19

COVID-19 pathogenesis is associated with an exaggerated immune response. However, the specific cellular mediators and inflammatory components driving diverse clinical disease outcomes remain poorly understood. We undertook longitudinal immune profiling on both whole blood and peripheral blood mononuclear cells of hospitalized patients during the peak of the COVID-19 pandemic in the United Kingdom. Here, we report key immune signatures present shortly after hospital admission that were associated with the severity of COVID-19. Immune signatures were related to shifts in neutrophil to T cell ratio, elevated serum IL-6, MCP-1, and IP-10 and modulation of CD14+ monocyte phenotype and function. Modified features of CD14+ monocytes included poor induction of the prostaglandin-producing enzyme, COX-2, and enhanced expression of the cell cycle marker Ki-67. Longitudinal analysis revealed reversion of some immune features back to the healthy median level in patients with a good eventual outcome. These findings identify previously unappreciated alterations in the innate immune compartment of patients with COVID-19 and lend support to the idea that therapeutic strategies targeting release of myeloid cells from bone marrow should be considered in this disease. Moreover, they demonstrate that features of an exaggerated immune response are present early after hospital admission, suggesting that immunomodulating therapies would be most beneficial at early time points

End-point effector stress mediators in neuroimmune interactions: their role in immune system homeostasis and autoimmune pathology

Much evidence has identified a direct anatomical and functional link between the brain and the immune system, with glucocorticoids (GCs), catecholamines (CAs), and neuropeptide Y (NPY) as its end-point mediators. This suggests the important role of these mediators in immune system homeostasis and the pathogenesis of inflammatory autoimmune diseases. However, although it is clear that these mediators can modulate lymphocyte maturation and the activity of distinct immune cell types, their putative role in the pathogenesis of autoimmune disease is not yet completely understood. We have contributed to this field by discovering the influence of CAs and GCs on fine-tuning thymocyte negative selection and, in particular, by pointing to the putative CA-mediated mechanisms underlying this influence. Furthermore, we have shown that CAs are implicated in the regulation of regulatory T-cell development in the thymus. Moreover, our investigations related to macrophage biology emphasize the complex interaction between GCs, CAs and NPY in the modulation of macrophage functions and their putative significance for the pathogenesis of autoimmune inflammatory diseases

Clinical manifestations of intermediate allele carriers in Huntington disease

Objective: There is controversy about the clinical consequences of intermediate alleles (IAs) in Huntington disease (HD). The main objective of this study was to establish the clinical manifestations of IA carriers for a prospective, international, European HD registry. Methods: We assessed a cohort of participants at risk with <36 CAG repeats of the huntingtin (HTT) gene. Outcome measures were the Unified Huntington's Disease Rating Scale (UHDRS) motor, cognitive, and behavior domains, Total Functional Capacity (TFC), and quality of life (Short Form-36 [SF-36]). This cohort was subdivided into IA carriers (27-35 CAG) and controls (<27 CAG) and younger vs older participants. IA carriers and controls were compared for sociodemographic, environmental, and outcome measures. We used regression analysis to estimate the association of age and CAG repeats on the UHDRS scores. Results: Of 12,190 participants, 657 (5.38%) with <36 CAG repeats were identified: 76 IA carriers (11.56%) and 581 controls (88.44%). After correcting for multiple comparisons, at baseline, we found no significant differences between IA carriers and controls for total UHDRS motor, SF-36, behavioral, cognitive, or TFC scores. However, older participants with IAs had higher chorea scores compared to controls (p 0.001). Linear regression analysis showed that aging was the most contributing factor to increased UHDRS motor scores (p 0.002). On the other hand, 1-year follow-up data analysis showed IA carriers had greater cognitive decline compared to controls (p 0.002). Conclusions: Although aging worsened the UHDRS scores independently of the genetic status, IAs might confer a late-onset abnormal motor and cognitive phenotype. These results might have important implications for genetic counseling. ClinicalTrials.gov identifier: NCT01590589